Brigatinib, with a chemical name of 5-chloro-N4-[2-(dimethylphosphonyl)phenyl]-N2-{2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}pyrimidine-2,4-diamine, is an anaplastic lymphoma kinase (AKL) inhibitor developed by ARIAD Pharmaceuticals, Inc, which can also inhibit EGFR and c-ros oncogene 1 (ROS1), and it thus can be used for treating ALK-positive non-small cell lung cancer and is currently in Phase II clinical trials. In October 2014, the US FDA granted its breakthrough therapeutic drug qualification. The results from Phase I/II clinical trials show that Brigatinib has persistent anti-tumor activity in patients with ALK-positive non-small cell lung cancer (including those with brain metastases).

Poor properties of absorption, distribution, metabolism and/or excretion (ADME) have been known as main reasons for failure of clinical trials of numerous drug candidates. The application ranges of many drugs currently on the market have been also limited due to their poor ADME properties. Rapid metabolism of drugs will cause many drugs, which could have treated diseases with high efficient, difficult to be prepared into medicine, due to excessively rapid metabolism and clearance from the body. Although the problem of the rapid clearance of drugs may be solved by frequent or high-dose administration, such approaches may present several problems, such as poor patient compliance, side effects caused by high-dose administration, increased therapy costs and the like. Furthermore, rapidly metabolized drugs may also expose patients to adverse toxicity or reactive metabolites.
Although Brigatinib as an inhibitor of ALK can effectively treat ALK-positive non-small cell lung cancer, it is still challenging to develop a novel compound which can treat ALK-positive non-small cell lung cancer and has good oral bioavailability and druggability. Therefore, there still is a need for the development of a compound suitable as a therapeutic agent with selective inhibition activity for anaplastic lymphoma kinase (AKL) or having better pharmacodynamics/pharmacokinetics in the art. The present invention provides such compounds.